MT-CYB

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External IDs	GeneCards: [1]
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Species	Human	Mouse
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RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
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File:Map of the human mitochondrial genome.svg

Location of the MT-CYB gene in the human mitochondrial genome (coral box).

Cytochrome b is a protein that in humans is encoded by the MT-CYB gene. Its gene product is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex), which consists of the products of one mitochondrially encoded gene, MT-CYB (mitochondrial cytochrome b) and ten nuclear genes: UQCRC1, UQCRC2, Cytochrome c1, UQCRFS1 (Rieske protein), UQCRB, "11kDa protein", UQCRH (cyt c1 Hinge protein), Rieske Protein presequence, "cyt. c1 associated protein", and Rieske-associated protein.

Structure

The MT-CYB gene is located on the p arm of mitochondrial DNA in position 12 and spans 1,140 base pairs. The gene produces a 42.7 kDa protein named cytochrome b composed of 380 amino acids. Cytochrome b is an integral membrane protein with hydrophobic properties. The catalytic core of the enzyme is composed of eight transmembrane helices, the iron-sulfur protein, and cytochrome c1. Cytochrome b is a fundamental component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. The structure of the complex is a symmetric homodimer. It is composed of eleven structural subunits, including one mitochondrial genome encoded cytochrome b and ten other nucleus encoded subunits. These subunits include 3 respiratory subunits (MT-CYB, CYC1 and UQCRFS1), 2 core proteins (UQCRC1 and UQCRC2) and 6 low-molecular weight proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and a cleavage product of UQCRFS1). The total molecular mass of the complex is about 450 kDa.

Function

The mitochondrial cytochrome b is fundamental for the assembly and function of Complex III of the mitochondrial respiratory chain. Complex III is responsible for the catalysis of electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain by translocating protons concomitantly across the inner membrane of the mitochondria. The transfer of electrons then contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis.

Clinical significance

Mutations in MT-CYB can result in mitochondrial deficiencies and associated disorders. It is majorly associated with a complex III deficiency, a deficiency in an enzyme complex which catalyzes electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain. A complex III deficiency can result in a highly variable phenotype depending on which tissues are affected. Most frequent clinical manifestations include progressive exercise intolerance and cardiomyopathy. Occasional multisystem disorders accompanied by exercise intolerance may arise as well, in forms of deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, and epilepsy. Other phenotypes include mitochondrial encephalomyopathy, mitochondrial myopathy, Leber hereditary optic neuropathy, muscle weakness, myoglobinuria, blood acidosis, renal tubulopathy, and more. Complex III deficiency is known to be rare among mitochondrial diseases and may follow a maternal or mendelian mode of inheritance due to its duality of genetic origin.

Further reading

• Ingman M, Kaessmann H, Pääbo S, Gyllensten U (Dec 2000). "Mitochondrial genome variation and the origin of modern humans". Nature. 408 (6813): 708–13. doi:10.1038/35047064. PMID 11130070.
• Maca-Meyer N, González AM, Larruga JM, Flores C, Cabrera VM (2003). "Major genomic mitochondrial lineages delineate early human expansions". BMC Genetics. 2: 13. doi:10.1186/1471-2156-2-13. PMC 55343. PMID 11553319.
• Herrnstadt C, Elson JL, Fahy E, Preston G, Turnbull DM, Anderson C, Ghosh SS, Olefsky JM, Beal MF, Davis RE, Howell N (May 2002). "Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups". American Journal of Human Genetics. 70 (5): 1152–71. doi:10.1086/339933. PMC 447592. PMID 11938495.
• Silva WA, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixão BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paçó-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA (Jul 2002). "Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America". American Journal of Human Genetics. 71 (1): 187–92. doi:10.1086/341358. PMC 384978. PMID 12022039.
• Yamasoba T, Goto Yi, Oka Y, Nishino I, Tsukuda K, Nonaka I (Jun 2002). "Atypical muscle pathology and a survey of cis-mutations in deaf patients harboring a 1555 A-to-G point mutation in the mitochondrial ribosomal RNA gene". Neuromuscular Disorders. 12 (5): 506–12. doi:10.1016/S0960-8966(01)00329-7. PMID 12031626.
• Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC (Jan 2003). "Natural selection shaped regional mtDNA variation in humans". Proceedings of the National Academy of Sciences of the United States of America. 100 (1): 171–6. doi:10.1073/pnas.0136972100. PMC 140917. PMID 12509511.
• Mancuso M, Filosto M, Stevens JC, Patterson M, Shanske S, Krishna S, DiMauro S (May 2003). "Mitochondrial myopathy and complex III deficiency in a patient with a new stop-codon mutation (G339X) in the cytochrome b gene". Journal of the Neurological Sciences. 209 (1–2): 61–3. doi:10.1016/S0022-510X(02)00462-8. PMID 12686403.
• Ingman M, Gyllensten U (Jul 2003). "Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines". Genome Research. 13 (7): 1600–6. doi:10.1101/gr.686603. PMC 403733. PMID 12840039.
• Kong QP, Yao YG, Sun C, Bandelt HJ, Zhu CL, Zhang YP (Sep 2003). "Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences". American Journal of Human Genetics. 73 (3): 671–6. doi:10.1086/377718. PMC 1180693. PMID 12870132.
• Kong QP, Yao YG, Liu M, Shen SP, Chen C, Zhu CL, Palanichamy MG, Zhang YP (Oct 2003). "Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China". Human Genetics. 113 (5): 391–405. doi:10.1007/s00439-003-1004-7. PMID 12938036.
• Maca-Meyer N, González AM, Pestano J, Flores C, Larruga JM, Cabrera VM (Oct 2003). "Mitochondrial DNA transit between West Asia and North Africa inferred from U6 phylogeography". BMC Genetics. 4: 15. doi:10.1186/1471-2156-4-15. PMC 270091. PMID 14563219.
• Haut S, de Villemeur TB, Brivet M, Guiochon-Mantel A, Boutron A, Rustin P, Legrand A, Slama A (Mar 2004). "The deleterious G15498A mutation in mitochondrial DNA-encoded cytochrome b may remain clinically silent in homoplasmic carriers". European Journal of Human Genetics. 12 (3): 220–4. doi:10.1038/sj.ejhg.5201132. PMID 14735157.
• Palanichamy MG, Sun C, Agrawal S, Bandelt HJ, Kong QP, Khan F, Wang CY, Chaudhuri TK, Palla V, Zhang YP (Dec 2004). "Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia". American Journal of Human Genetics. 75 (6): 966–78. doi:10.1086/425871. PMC 1182158. PMID 15467980.
• Starikovskaya EB, Sukernik RI, Derbeneva OA, Volodko NV, Ruiz-Pesini E, Torroni A, Brown MD, Lott MT, Hosseini SH, Huoponen K, Wallace DC (Jan 2005). "Mitochondrial DNA diversity in indigenous populations of the southern extent of Siberia, and the origins of Native American haplogroups". Annals of Human Genetics. 69 (Pt 1): 67–89. doi:10.1046/j.1529-8817.2003.00127.x. PMC 3905771. PMID 15638829.
• Rajkumar R, Banerjee J, Gunturi HB, Trivedi R, Kashyap VK (2006). "Phylogeny and antiquity of M macrohaplogroup inferred from complete mt DNA sequence of Indian specific lineages". BMC Evolutionary Biology. 5: 26. doi:10.1186/1471-2148-5-26. PMC 1079809. PMID 15804362.
• Thangaraj K, Chaubey G, Kivisild T, Reddy AG, Singh VK, Rasalkar AA, Singh L (May 2005). "Reconstructing the origin of Andaman Islanders". Science. 308 (5724): 996. doi:10.1126/science.1109987. PMID 15890876.
• Blakely EL, Mitchell AL, Fisher N, Meunier B, Nijtmans LG, Schaefer AM, Jackson MJ, Turnbull DM, Taylor RW (Jul 2005). "A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast". The FEBS Journal. 272 (14): 3583–92. doi:10.1111/j.1742-4658.2005.04779.x. PMID 16008558.
• Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, Scozzari R, Modiano D, Coppa A, de Knijff P, Feldman M, Cavalli-Sforza LL, Oefner PJ (Jan 2006). "The role of selection in the evolution of human mitochondrial genomes". Genetics. 172 (1): 373–87. doi:10.1534/genetics.105.043901. PMC 1456165. PMID 16172508.
• Behar DM, Metspalu E, Kivisild T, Achilli A, Hadid Y, Tzur S, Pereira L, Amorim A, Quintana-Murci L, Majamaa K, Herrnstadt C, Howell N, Balanovsky O, Kutuev I, Pshenichnov A, Gurwitz D, Bonne-Tamir B, Torroni A, Villems R, Skorecki K (Mar 2006). "The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event". American Journal of Human Genetics. 78 (3): 487–97. doi:10.1086/500307. PMC 1380291. PMID 16404693.
• van Holst Pellekaan SM, Ingman M, Roberts-Thomson J, Harding RM (Oct 2006). "Mitochondrial genomics identifies major haplogroups in Aboriginal Australians". American Journal of Physical Anthropology. 131 (2): 282–94. doi:10.1002/ajpa.20426. PMID 16596590.